Search results for: antiepileptic drugs

Authors: Narin Ozturk, Xiao-Mei Li, Sylvie Giachetti, Francis Levi, Alper Okyar

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P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, mdr1a::Luc mice, p-glycoprotein

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Authors: Khaled Sekkoum

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The traditional pharmacopoeia of Algerian Sahara is very rich on vegetable drugs. The great resources and biodiversity of Algerian Sahara flora seem responsible. A survey of medicinal plants used by the local population of the south west of Algeria for the urinary disorders is reported. Sixty-three plant species belonging to thirty-three families were identified. Their botanical and local names, plant part used, mode of use and ailment treated are given.

Keywords: medicinal plants, urinary diseases, Sahara, Algeria

Procedia PDF Downloads 334

Authors: Abeer N. Alshukairi, Abdulrahman A. Alrajhi, Abdulfattah W. Alamri, Adel F. Alothman

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We described the nosocomial transmission of a pre-XDR or an MDR case of pulmonary tuberculosis in a HIV negative health care worker in an area endemic for MDR & XDR tuberculosis. With inadequate therapy and non-compliance, his strain developed acquired resistance and he presented with extra-pulmonary XDR tuberculosis in the form of multi-focal osteomyelitis and encysted pleural effusion. He was cured after 2 years of therapy with various anti-tuberculous drugs in addition to interferon gamma.

Keywords: osteomyelitis, treatment, XDR tuberculosis, successful treatment

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Authors: Asiya Mahtab, Sushama Talegaonkar

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The research is aimed at developing targeted lipid-based nanocarrier systems of chondroitin sulfate (CS) to deliver an antirheumatic drug to the inflammatory site in arthritic paw. Lipid-based nanoparticle (TEF-lipo) was prepared by using a thin-film hydration method. The coating of prepared drug-loaded nanoparticles was done by the ionic interaction mechanism. TEF-lipo and CS-coated lipid nanoparticle (CS-lipo) were characterized for mean droplet size, zeta potential, and surface morphology. TEF-lipo and CS-lipo were further subjected to in vitro cell line studies on RAW 264.7 murine macrophage, U937, and MG 63 cell lines. The pharmacodynamic study was performed to establish the effectiveness of the prepared lipid-based conventional and targeted nanoparticles in comparison to pure drugs. Droplet size and zeta potential of TEF-lipo were found to be 128. 92 ± 5.42 nm and +12.6 ± 1.2 mV. It was observed that after the coating of TEF-lipo with CS, particle size increased to 155.6± 2.12 nm and zeta potential changed to -10.2± 1.4mV. Transmission electron microscopic analysis revealed that the nanovesicles were uniformly dispersed and detached from each other. Formulations followed sustained release pattern up to 24 h. Results of cell line studies ind icated that CS-lipo formulation showed the highest cytotoxic potential, thereby proving its enhanced ability to kill the RAW 264.7 murine macrophage and U937 cells when compared with other formulations. It is clear from our in vivo pharmacodynamic results that targeted nanocarriers had a higher inhibitory effect on arthritis progression than nontargeted nanocarriers or free drugs. Results demonstrate that this approach will provide effective treatment for rheumatoid arthritis, and CS served as a potential prophylactic against the advancement of cartilage degeneration.

Keywords: adjuvant induced arthritis, chondroitin sulfate, rheumatoid arthritis, teriflunomide

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Authors: Maria I. Nuñez-Hernández, Maria L. Riesco

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Background: Exclusive breastfeeding (EBF) up to 6 months old infant have been considered one of the most important factors in the overall development of children. Nevertheless, as resources are scarce, it is essential to identify the most vulnerable groups that have major risk of EBF abandonment, in order to deliver the best strategies. Children of adolescent mothers are within these groups. Aims: To determine the EBF abandonment rate among adolescent mothers and to analyze the associated factors. Methods: Prospective cohort study of adolescent mothers in the southern area of Santiago, Chile, conducted in primary care services of public health system. The cohort was established from 2014 to 2015, with a sample of 105 adolescent mothers and their children at 2 months of life. The inclusion criteria were: adolescent mother from 14 to 19 years old; not twin babies; mother and baby leaving the hospital together after birthchild; correct attachment of the baby to the breast; no difficulty understanding the Spanish language or communicating. Follow-up was performed at 4 and 6 months old infant. Data were collected by interviews, considering EBF as breastfeeding only, without adding other milk, tea, juice, water or other product that not breast milk, except drugs. Data were analyzed by descriptive and inferential statistics, by Kaplan-Meier estimator and Log-Rank test, admitting the probability of occurrence of type I error of 5% (p-value = 0.05). Results: The cumulative EBF abandonment rate at 2, 4 and 6 months was 33.3%, 52.2% and 63.8%, respectively. Factors associated with EBF abandonment were maternal perception of the quality of milk as poor (p < 0.001), maternal perception that the child was not satisfied after breastfeeding (p < 0.001), use of pacifier (p < 0.001), maternal consumption of illicit drugs after delivery (p < 0.001), mother return to school (p = 0.040) and presence of nipple trauma (p = 0.045). Conclusion: EBF abandonment rate was higher in the first 4 months of life and is superior to the population of women who breastfeed. Among the EBF abandonment factors, one of them is related to the adolescent condition, and two are related to the maternal subjective perception.

Keywords: adolescent, breastfeeding, midwifery, nursing

Procedia PDF Downloads 321

Authors: Akhtar Aman, Abida Raza, Shumaila Bashir, Javaid Irfan, Andreas G. Schätzlein, Ijeoma F Uchegbeu

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Development of efficient delivery system for hydrophobic drugs remains a major concern in chemotherapy. The objective of the current study was to develop polymeric drug-delivery system for etoposide from amphiphilic derivatives of glycol chitosan, capable to improve the pharmacokinetics and to reduce the adverse effects of etoposide due to various organic solvents used in commercial formulations for solubilisation of etoposide. As a promising carrier, amphiphilic derivatives of glycol chitosan were synthesized by chemical grafting of palmitic acid N-hydroxy succinimide and quaternisation to glycol chitosan backbone. To this end a 7.9 kDa glycol chitosan was modified by palmitoylation and quaternisation into 13 kDa. Nano sized micelles prepared from this amphiphilic polymer had the capability to encapsulate up to 3 mg/ml etoposide. The pharmacokinetic results indicated that GCPQ based etoposide formulation transformed the biodistribution pattern. AUC 0.5-24 hr showed statistically significant difference in ETP-GCPQ vs. commercial preparation in liver (25 vs 70, p<0.001), spleen (27 vs. 36, P<0.05), lungs (42 vs. 136, p<0.001), kidneys (25 vs. 30, p<0.05) and brain (19 vs. 9,p<0.001). Using the hydrophobic fluorescent dye Nile red, we showed that micelles efficiently delivered their payload to MCF7 and A2780 cancer cells in-vitro and to A431 xenograft tumor in-vivo, suggesting these systems could deliver hydrophobic anti- cancer drugs such as etoposide to tumors. The pharmacokinetic results indicated that the GCPQ micelles transformed the biodistribution pattern and increased etoposide concentration in the brain significantly compared to free drug after intravenous administration. GCPQ based formulations not only reduced side effects associated with current available formulations but also increased their transport through the biological barriers, thus making it a good delivery system.

Keywords: glycol chitosan, Nile red, micelles, etoposide, A431 xenografts

Procedia PDF Downloads 310

Authors: Anika Chebrolu

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Mono-targeted drugs can be of limited efficacy against complex diseases. Recently, multi-target drug design has been approached as a promising tool to fight against these challenging diseases. However, the scope of current computational approaches for multi-target drug design is limited. DeepLig presents a de-novo drug discovery platform that uses reinforcement learning to generate and optimize novel, potent, and multitargeted drug candidates against protein targets. DeepLig’s model consists of two networks in interplay: a generative network and a predictive network. The generative network, a Stack- Augmented Recurrent Neural Network, utilizes a stack memory unit to remember and recognize molecular patterns when generating novel ligands from scratch. The generative network passes each newly created ligand to the predictive network, which then uses multiple Graph Attention Networks simultaneously to forecast the average binding affinity of the generated ligand towards multiple target proteins. With each iteration, given feedback from the predictive network, the generative network learns to optimize itself to create molecules with a higher average binding affinity towards multiple proteins. DeepLig was evaluated based on its ability to generate multi-target ligands against two distinct proteins, multi-target ligands against three distinct proteins, and multi-target ligands against two distinct binding pockets on the same protein. With each test case, DeepLig was able to create a library of valid, synthetically accessible, and novel molecules with optimal and equipotent binding energies. We propose that DeepLig provides an effective approach to design multi-targeted drug therapies that can potentially show higher success rates during in-vitro trials.

Keywords: drug design, multitargeticity, de-novo, reinforcement learning

Procedia PDF Downloads 97

Authors: Syed Benazir Firdaus, Debosree Ghosh, Aindrila Chattyopadhyay, Kuladip Jana, Debasish Bandyopadhyay

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Gastro-toxic effect of piroxicam, a classical non-steroidal anti-inflammatory drug (NSAID), has restricted its use in arthritis and similar diseases. The present study aims to find if a combination of melatonin and Murraya koenigii leaf extract therapy can protect against piroxicam induced ulcerative damage in rats. For this study, rats were divided into four groups namely control group where rats were orally administered distilled water, only combination treated group, piroxicam treated group and combination pre-administered piroxicam treated group. Each group of rats consisted of six animals. Melatonin at a dose of 20mg/kg body weight and antioxidant rich Murraya koenigii leaf extract at a dose of 50 mg /kg body weight were successively administered at 30 minutes interval one hour before oral administration of piroxicam at a dose of 30 mg/kg body weight to Wistar rats in the combination pre-administered piroxicam treated group. The rats of the animal group which was only combination treated were administered both the drugs respectively without piroxicam treatment whereas the piroxicam treated animal group was administered only piroxicam at 30mg/kg body weight without any pre-treatment with the combination. Macroscopic examination along with histo-pathological study of gastric tissue using haemotoxylin-eosin staining and alcian blue dye staining showed protection of the gastric mucosa in the combination pre-administered piroxicam treated group. Determination of adherent mucus content biochemically and collagen content through Image J analysis of picro-sirius stained sections of rat gastric tissue also revealed protective effects of the combination in piroxicam mediated toxicity. Gelatinolytic activity of piroxicam was significantly reduced by pre-administration of the drugs which was well exhibited by the gelatin zymography study of the rat gastric tissue. Mean ulcer index determined from macroscopic study of rat stomach reduced to a minimum (0±0.00; Mean ± Standard error of mean and number of animals in the group=6) indicating the absence of ulcer spots on pre-treatment of rats with the combination. Gastro-friendly prostaglandin (PGE2) which otherwise gets depleted on piroxicam treatment was also well protected when the combination was pre-administered in the rats prior to piroxicam treatment. The requirement of the individual drugs in low doses in this combinatorial therapeutic approach will possibly minimize the cost of therapy as well as it will eliminate the possibility of any pro-oxidant side effects on the use of high doses of antioxidants. Beneficial activity of this combination therapy in the rat model raises the possibility that similar protective actions might be also observed if it is adopted by patients consuming NSAIDs like piroxicam. However, the introduction of any such therapeutic approach is subject to future studies in human.

Keywords: gastro-protective action, melatonin, Murraya koenigii leaf extract, piroxicam

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Authors: Abhishek Pandey

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Ibuprofen and Acetaminophen is widely used as prescription & non-prescription medicine. Ibuprofen mainly used in the treatment of mild to moderate pain related to headache, migraine, postoperative condition and in the management of spondylitis, osteoarthritis and rheumatoid arthritis. Acetaminophen is used as an analgesic and antipyretic drug. Ibuprofen having high tendency of sticking to punches of tablet punching machine while Acetaminophen is not ordinarily compressible to tablet formulation because Acetaminophen crystals are very hard and brittle in nature and fracture very easily when compressed producing capping and laminating tablet defects therefore wet granulation method is used to make them compressible. The aim of study was to prepare Ibuprofen and Acetaminophen tablets by direct compression and top spray granulation technique. In this Investigation tablets were prepared by using directly compressible grade excipients. Dibasic calcium phosphate, lactose anhydrous (DCL21), microcrystalline cellulose (Avicel PH 101). In order to obtain best or optimized formulation, nine different formulations were generated among them batch F7, F8, F9 shows good results and within the acceptable limit. Formulation (F7) selected as optimize product on the basis of dissolution study. Furtherly, directly compressible granules of both drugs were prepared by using top spray granulation technique in fluidized bed processor equipment and compressed .In order to obtain best product process optimization was carried out by performing four trials in which various parameters like inlet air temperature, spray rate, peristaltic pump rpm, % LOD, properties of granules, blending time and hardness were optimized. Batch T3 coined as optimized batch on the basis physical & chemical evaluation. Finally formulations prepared by both techniques were compared.

Keywords: direct compression, top spray granulation, process optimization, blending time

Procedia PDF Downloads 362

Authors: Garzon V., Bustos R., Salvador J. P., Marco M. P., Pinacho D. G.

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Bacterial resistance to antimicrobial treatment has increased significantly in recent years, making it a public health problem. Large numbers of bacteria are resistant to all or nearly all known antimicrobials, creating the need for the development of new types of antimicrobials or the use of “last line” antimicrobial drug therapies for the treatment of multi-resistant bacteria. Some of the chemical groups of antimicrobials most used for the treatment of infections caused by multiresistant bacteria in the clinic are Glycopeptide (Vancomycin), Polymyxin (Colistin), Lipopeptide (Daptomycin) and Carbapenem (Meropenem). Molecules that require therapeutic drug monitoring (TDM). Due to the above, a methodology based on nanobiotechnology based on an optical and electrochemical biosensor is being developed, which allows the evaluation of the plasmatic levels of some antimicrobials such as glycopeptide, polymyxin, lipopeptide and carbapenem quickly, at a low cost, with a high specificity and sensitivity and that can be implemented in the future in public and private health hospitals. For this, the project was divided into five steps i) Design of specific anti-drug antibodies, produced in rabbits for each of the types of antimicrobials, evaluating the results by means of an immunoassay analysis (ELISA); ii) quantification by means of an electrochemical biosensor that allows quantification with high sensitivity and selectivity of the reference antimicrobials; iii) Comparison of antimicrobial quantification with an optical type biosensor; iv) Validation of the methodologies used with biosensor by means of an immunoassay. Finding as a result that it is possible to quantify antibiotics by means of the optical and electrochemical biosensor at concentrations on average of 1,000ng/mL, the antibodies being sensitive and specific for each of the antibiotic molecules, results that were compared with immunoassays and HPLC chromatography. Thus, contributing to the safe use of these drugs commonly used in clinical practice and new antimicrobial drugs.

Keywords: antibiotics, electrochemical biosensor, optical biosensor, therapeutic drug monitoring

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Authors: Rajendra Jangde, Deependra Singh

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Present work was based with objective to release of the antimicrobial and debriding agent in sustained manner at the wound surface. In order to provide a long-lasting antimicrobial action and moist environment on wound space, Biocompatible moist system was developed for complete healing. In the present study, a biocompatible moist system of PVA-gelatin hydrogel was developed capable of carrying multiple drugs- Quercetin and Cabopol in controlled manner for effective and complete wound healing. Carbopol and Quercetin were prepared by thin film hydration techniques and optimized system was incorporated in PVA-Gelatin slurry. PVA-Gelatin hydrogels were prepared by freeze thaw method. The prepared dispersion was casted into films to prepare multiphase hydrogel system and characterized by in vitro and in vivo studies. Results revealed the uniform dispersion of microspheres in a three-dimensional matrix of the PVA-Gelatin hydrogel observed at different magnifications. The in vitro release data showed typical biphasic release pattern, i.e., a burst release followed by a slower sustained release for 5 days. Prepared system was found to be stable under both normal and accelerated conditions. Histopathological study showed significant (p<0.05) increase in fibroblast cells, collagen fibres and blood vessels formation. All parameters such as wound contraction, tensile strength, histopathological and biochemical parameters- hydroxyproline content, protein level, etc. were observed significant (p<0.05) in comparison to control group. Present results suggest an accelerated re-epithelialization under moist wound environment with delivery of multiple drugs effective at different stages of wound healing cascade with minimum disturbance of wound bed.

Keywords: multiphase hydrogel, optimization quercetin, wound healing

Procedia PDF Downloads 240

Authors: Chukwudalu C. Nwazojie, Wole W. Soboyejo, John Obayemi, Ali Salifu Azeko, Sandra M. Jusu, Chinyerem M. Onyekanne

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The conventional methods for the diagnosis and treatment of breast cancer include bulk systematic mammography, ultrasound, dynamic contrast-enhanced fast 3D gradient-echo (GRE) magnetic resonance imaging (MRI), surgery, chemotherapy, and radiotherapy. However, nanoparticles and drug-loaded polymer microspheres for disease (cancer) targeting and treatment have enormous potential to enhance the approaches that are used today. The goal is to produce an implantable biomedical device for localized breast cancer drug delivery within Africa and the world. The main advantage of localized delivery is that it reduces the amount of drug that is needed to have a therapeutic effect. Polymer blends of poly (D,L-lactide-co-glycolide) (PLGA) and polycaprolactone (PCL), which are biodegradable, is used as a drug excipient. This work focuses on the development of PLGA-PCL (poly (D,L-lactide-co-glycolide) (PLGA) blended with based injectable drug microspheres and are loaded with anticancer drugs (prodigiosin (PG), and paclitaxel (PTX) control) and also the conjugated forms of the drug functionalized with LHRH (luteinizing hormone-releasing hormone) (PG-LHRH, and PTX- LHRH control), using a single-emulsion solvent evaporation technique. The encapsulation was done in the presence of PLGA-PCL (as a polymer matrix) and poly-(vinyl alcohol) (PVA) (as an emulsifier). Comparative study of the various drugs release kinetics and degradation mechanisms of the PLGA-PCL with an encapsulated drug is achieved, and the implication of this study is for the potential application of prodigiosin PLGA-PCL loaded microparticles for controlled delivery of cancer drug and treatment to prevent the regrowth or locoregional recurrence, following surgical resection of triple-negative breast tumor.

Keywords: cancer, polymers, drug kinetics, nanoparticles

Procedia PDF Downloads 100

Authors: Godwin Ojochogu Adejo, Evelyn UnekwuOjo Adejo, Sunday UnenwOjo Adejo

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The mainstream contemporary approach to controlling the impact of diseases among poultry birds rely largely on curative measures through the administration of drugs to infected birds. Most times as observed in the deep liter poultry farming system, entire flocks including uninfected birds receive the treatment they do not need. As such, unguarded use of chemical drugs and antibiotics has led to wastage and accumulation of chemical residues in poultry products with associated health hazards to humans. However, wanton and frequent drug usage in poultry is avoidable if feeding and drinking equipment are designed to curb infection transmission among birds. Using toxicological assays as guide and with efficiency and simplicity in view, two newly field-tested and recently patented equipments called 'healthy liquid drinking trough (HDT)' and 'healthy feeding trough (HFT)' that systematically eliminate contamination of the feeding and drinking channels, thereby, curbing wide-spread infection and transmission of diseases in the (intensive) deep litter poultry farming system were designed. Upon combined usage, they automatically and drastically reduced both the amount and frequency of antibiotics use in poultry by over > 50%. Additionally, they conferred optimization of feed and water utilization/elimination of wastage by > 80%, reduced labour by > 70%, reduced production cost by about 15%, and reduced chemical residues in poultry meat or eggs by > 85%. These new and cheap technologies which require no energy input are likely to elevate safety of poultry products for consumers' health, increase marketability locally and for export, and increase output and profit especially among poultry farmers and poor people who keep poultry or inevitably utilize poultry products in developing countries.

Keywords: healthy, trough, toxicological, assay-guided, poultry

Procedia PDF Downloads 155

Authors: A. Adetutu, T. M. Awodugba, O. A. Owoade

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The development of resistance to currently known conventional anti-typhoid drugs has necessitated search into cheap, more potent and less toxic anti-typhoid drugs of plant origin. Therefore, this study investigated the anti-typhoid activity of fractions of A. indica in Salmonella typhi infected rats. Leaves of A. indica were extracted in methanol and fractionated into n-hexane, chloroform, ethyl-acetate, and aqueous fractions. The anti-salmonella potentials of fractions of A. indica were assessed via in-vitro inhibition of S. typhi using agar well diffusion, Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and biofilm assays. The biochemical and haematological parameters were determined by spectrophotometric methods. The histological analysis was performed using Haematoxylin and Eosin staining methods. Data analysis was performed by one-way ANOVA. Results of this study showed that S. typhi was sensitive to aqueous and chloroform fractions of A. indica, and the fractions showed biofilm inhibition at concentrations of 12.50, 1.562, and 0.39 mg/mL. In the in-vivo study, the extract and chloroform fraction had significant (p < 0.05) effects on the number of viable S. typhi recovered from the blood and stopped salmonellosis after 6 days of treatment of rats at 500 mg/kg b.w. Treatments of infected rats with chloroform and aqueous fractions of A. indica normalized the haematological parameters in the animals. Similarly, treatment with fractions of the plants sustained a normal antioxidant status when compared with the normal control group. Chloroform and ethyl-acetate fractions of A. indica reversed the liver and intestinal degeneration induced by S. typhi infection in rats. The present investigation indicated that the aqueous and chloroform fractions of A. indica showed the potential to provide an effective treatment for salmonellosis, including typhoid fever. The results of the study may justify the ethno-medicinal use of the extract in traditional medicine for the treatment of typhoid and salmonella infections.

Keywords: Azadirachta indica L, salmonella, typhoid, leave fractions

Procedia PDF Downloads 132

Authors: V. S. Bessa, I. S. Moreira, S. Murgolo, C. Piccirillo, G. Mascolo, P. M. L. Castro

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The occurrence of pharmaceuticals in the environment has been a topic of increasing concern. Pharmaceuticals are not completely mineralized in the human body and are released on the sewage systems as the pharmaceutical itself and as their “biologically active” metabolites through excretion, as well as by improper elimination and disposal. Conventional wastewater treatment plants (WWTPs) are not designed to remove these emerging pollutants and they are thus released into the environment. The antiepileptic drug carbamazepine (CBZ) and the non-steroidal anti-inflammatory diclofenac (DCF) are two widely used pharmaceuticals, frequently detected in water bodies, including rivers and groundwater, in concentrations ranging from ng L 1 to mg L 1. These two compounds were classified as medium to high-risk pollutants in WWTP effluents and surface waters. Also, CBZ has been suggested as a molecular marker of wastewater contamination in surface water and groundwater and the European Union included DCF in the watch list of substances Directive to be monitored. In the present study, biodegradation of CBZ and DCF by the bacterial strain Labrys portucalensis F11, a strain able to degrade other pharmaceutical compounds, was assessed; tests were performed with F11 as single carbon and energy source, as well as in presence of 5.9mM of sodium acetate. In assays supplemented with 2.0 and 4.0 µM of CBZ, the compound was no longer detected in the bulk medium after 24hr and 5days, respectively. Complete degradation was achieved in 21 days for 11.0 µM and in 23 days for 21.0 µM. For the highest concentration tested (43.0 µM), 95% of degradation was achieved in 30days. Supplementation with acetate increased the degradation rate of CBZ, for all tested concentrations. In the case of DCF, when supplemented as a single carbon source, approximately 70% of DCF (1.7, 3.3, 8.4, 17.5 and 34.0 µM) was degraded in 30days. Complete degradation was achieved in the presence of acetate for all tested concentrations, at higher degradation rates. The detection of intermediates produced during DCF biodegradation was performed by UPLC-QTOF/MS/MS, which allowed the identification of a range of metabolites. Stoichiometric liberation of chorine occurred and no metabolites were detected at the end of the biodegradation assays suggesting a complete mineralization of DCF. Strain Labrys portucalensis F11 proved to be able to degrade these two top priority environmental contaminants and may be potentially useful for biotechnological applications/environment remediation.

Keywords: biodegradation, carbamazepine, diclofenac, pharmaceuticals

Procedia PDF Downloads 273

Authors: K. Srujana, Vinay U. Rao, M. Sudhakar

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Isoniazide (INH) a freely water soluble and pyrazinamide (Z) a practically water insoluble first line anti tubercular (TB) drugs were identified as candidates for optimizing the Moisture Activated Dry Granulation (MADG) process. The work focuses on identifying the effect of binder type and concentration as well as the effect of magnesium stearate level on critical quality attributes of Disintegration time (DT) and in vitro dissolution test when the tablets are processed by the MADG process. Also, the level of the drug concentration, binder concentration and fluid addition during the agglomeration stage of the MADG process was evaluated and optimized. For INH, it was identified that for tablets with HPMC as binder at both 2% w/w and 5% w/w level and Magnesium stearate upto 1%w/w as lubrication the DT is within 1 minute and the dissolution rate is the fastest (> 80% in 15 minutes) as compared to when PVP or pregelatinized starch is used as binder. Regarding the process, fast disintegrating and rapidly dissolving tablets are obtained when the level of drug, binder and fluid uptake in agglomeration stage is 25% w/w 0% w/w binder and 0.033%. w/w. At the other 2 levels of these three ingredients, the DT is significantly impacted and dissolution is also slower. For pyrazinamide,it was identified that for the tablets with 2% w/w level of each of PVP as binder and Cross Caramellose Sodium disintegrant the DT is within 2 minutes and the dissolution rate is the fastest(>80 in 15 minutes)as compared to when HPMC or pregelatinized starch is used as binder. This may be attributed to the fact that PVP may be acting as a solubilizer for the practically insoluble Pyrazinamide. Regarding the process,fast dispersing and rapidly disintegrating tablets are obtained when the level of drug, binder and fluid uptake in agglomeration stage is 10% w/w,25% w/w binder and 1% w/w.At the other 2 levels of these three ingredients, the DT is significantly impacted and dissolution is comparatively slower and less complete.

Keywords: agglomeration stage, isoniazide, MADG, moisture distribution stage, pyrazinamide

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Authors: Rodchares Hanrinth, Theerapong Srisil, Peeraya Sriphong, Pawich Paktipat

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The trigger tool is the low-cost, low-tech method to detect adverse events through clues called triggers. The Institute for Healthcare Improvement (IHI) has developed the Global Trigger Tool for measuring and preventing adverse events. However, this tool is not specific for detecting adverse drug events. The pharmacy-based trigger tool is needed to detect adverse drug events (ADEs). Group concept mapping is an effective method for conceptualizing various ideas from diverse stakeholders. This technique was used to identify a pharmacy-based trigger to detect adverse drug events (ADEs). The aim of this study was to involve the pharmacists in conceptualizing, developing, and prioritizing a feasible trigger tool to detect adverse drug events in a provincial hospital, the northeastern part of Thailand. The study was conducted during the 6-month period between April 1 and September 30, 2017. Study participants involved 20 pharmacists (17 hospital pharmacists and 3 pharmacy lecturers) engaging in three concept mapping workshops. In this meeting, the concept mapping technique created by Trochim, a highly constructed qualitative group technic for idea generating and sharing, was used to produce and construct participants' views on what triggers were potential to detect ADEs. During the workshops, participants (n = 20) were asked to individually rate the feasibility and potentiality of each trigger and to group them into relevant categories to enable multidimensional scaling and hierarchical cluster analysis. The outputs of analysis included the trigger list, cluster list, point map, point rating map, cluster map, and cluster rating map. The three workshops together resulted in 21 different triggers that were structured in a framework forming 5 clusters: drug allergy, drugs induced diseases, dosage adjustment in renal diseases, potassium concerning, and drug overdose. The first cluster is drug allergy such as the doctor’s orders for dexamethasone injection combined with chlorpheniramine injection. Later, the diagnosis of drug-induced hepatitis in a patient taking anti-tuberculosis drugs is one trigger in the ‘drugs induced diseases’ cluster. Then, for the third cluster, the doctor’s orders for enalapril combined with ibuprofen in a patient with chronic kidney disease is the example of a trigger. The doctor’s orders for digoxin in a patient with hypokalemia is a trigger in a cluster. Finally, the doctor’s orders for naloxone with narcotic overdose was classified as a trigger in a cluster. This study generated triggers that are similar to some of IHI Global trigger tool, especially in the medication module such as drug allergy and drug overdose. However, there are some specific aspects of this tool, including drug-induced diseases, dosage adjustment in renal diseases, and potassium concerning which do not contain in any trigger tools. The pharmacy-based trigger tool is suitable for pharmacists in hospitals to detect potential adverse drug events using clues of triggers.

Keywords: adverse drug events, concept mapping, hospital, pharmacy-based trigger tool

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Authors: Michelle V. Tomczak, Reyhaneh Bakhtiari, Aaron Granley, Anthony Singhal

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Objective: Cannabis and cocaine are associated with a range of mental and physical effects that can impair aspects of human behavior. Driving is a complex cognitive behavior that is an essential part of everyday life and can be broken down into many subcomponents, each of which can uniquely impact road safety. With the growing movement of jurisdictions to legalize cannabis, there is an increased focus on impairment and driving. The purpose of this study was to identify driving-related cognitive-performance deficits that are impacted by recreational drug use. Design and Methods: With the assistance of law enforcement agencies, we recruited over 300 participants under the influence of various drugs including cannabis and cocaine. These individuals performed a battery of computer-based tasks scientifically proven to be re-lated to on-road driving performance and designed to test response-speed, memory processes, perceptual-motor skills, and decision making. Data from a control group with healthy non-drug using adults was collected as well. Results: Compared to controls, the drug group showed def-icits in all tasks. The data also showed clear differences between the cannabis and cocaine groups where cannabis users were faster, and performed better on some aspects of the decision-making and perceptual-motor tasks. Memory performance was better in the cocaine group for simple tasks but not more complex tasks. Finally, the participants who consumed both drugs performed most similarly to the cannabis group. Conclusions: Our results show distinct and combined effects of cannabis and cocaine on human performance relating to driving. These dif-ferential effects are likely related to the unique effects of each drug on the human brain and how they distinctly contribute to mental states. Our results have important implications for road safety associated with driver impairment.

Keywords: driving, cognitive impairment, recreational drug use, cannabis and cocaine

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Authors: Sweta Agrawal, Sachin Chaugule, Gargi Rane, Shashank More, Madhavi Indap

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Angiogenesis and metastasis are two of the most important hallmarks of cancer. Hence, most of the cancer therapies nowadays are multi-targeted so as to reduce resistance and have better efficacy. As synthetic molecules arise with a burden of their toxicities and side-effects, more and more research is being focussed on exploiting the vast natural resources of drugs, in the form of plants and animals. Although, the idea of using marine organisms as a source of pharmaceuticals is not new, the pace at which marine drugs are being discovered, has definitely up surged! In the present study, we have assessed the anti-angiogenic and in vitro anti-metastatic activity of aqueous fraction from the extract of marine gastropod Euchelus asper. The soft body of Euchelus Asper was extracted with methanol and named EAME. Partition chromatography of EAME gave three fractions EAME I, II and III. Biochemical analysis revealed the presence of proteins in EAME III. Preliminary analysis had revealed the anti-angiogenic activity was exhibited by EAME III out of the three fractions. Hereafter, EAME III (concentration 25µg/ml-400µg/ml) was tested on chick chorioallantoic membrane (CAM) model for the detailed analysis of its potential anti-angiogenic effect. In vitro testing of the fraction (concentration 0.25µg/ml - 1µg/ml), involved cytotoxicity by SRB assay, cell cycle analysis by flow cytometry and anti-proliferative effect by scratch wound healing assay on A549 lung carcinoma cells. Apart from this, a portion of treated CAM as well as conditioned medium from treated A549 were subjected to gelatin zymography for assessment of matrix metalloproteinases MMP-2 and MMP-9 levels. Our results revealed that EAME III exhibited significant anti-angiogenic activity on CAM which was also supported by histological observations. During histological studies of CAM, it was found that EAME III caused reduction in angiogenesis by altering the extracellular matrix of the CAM membrane. In vitro analysis disclosed that EAME III exhibited moderate cytotoxic effect on A549 cells and its effect was not dose-dependent. The results of flow cytometry confirmed that EAME III caused cell cycle arrest in A549 cell line as almost all of the treated cells were found in G1 phase. Further, the migration and proliferation of A549 was significantly reduced by EAME III as observed from the scratch wound assay. Moreover, Gelatin zymography analysis revealed that EAME III caused suppression of MMP-2 in CAM membrane and reduced MMP-9 and MMP-2 expression in A549 cells. This verified that the anti-angiogenic and anti-metastatic effects of EAME III were correlated with the suppression of MMP-2 and -9. To conclude, EAME III shows dual anti-tumour action by reducing angiogenesis and exerting anti-metastatic effect on lung cancer cells, thus it has the potential to be used as an anti-cancer agent against lung carcinoma.

Keywords: angiogenesis, anti-cancer, marine drugs, matrix metalloproteinases

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Authors: Shaista Suhail

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As cancer populations is increasing sharply, the incidence of oral squamous cell carcinoma (OSCC) has also been expected to increase. Oral carcinogenesis is a highly complex, multistep process which involves accumulation of genetic alterations that lead to the induction of proteins promoting cell growth (encoded by oncogenes), increased enzymatic (telomerase) activity promoting cancer cell proliferation. The global increase in frequency and mortality, as well as the poor prognosis of oral squamous cell carcinoma, has intensified current research efforts in the field of prevention and early detection of this disease. The advances in the understanding of the molecular basis of oral cancer should help in the identification of new markers. The study of the carcinogenic process of the oral cancer, including continued analysis of new genetic alterations, along with their temporal sequencing during initiation, promotion and progression, will allow us to identify new diagnostic and prognostic factors, which will provide a promising basis for the application of more rational and efficient treatments. Telomerase activity has been readily found in most cancer biopsies, in premalignant lesions or germ cells. Activity of telomerase is generally absent in normal tissues. It is known to be induced upon immortalization or malignant transformation of human cells such as in oral cancer cells. Maintenance of telomeres plays an essential role during transformation of precancer to malignant stage. Mammalian telomeres, a specialized nucleoprotein structures are composed of large conctamers of the guanine-rich sequence 5_-TTAGGG-3_. The roles of telomeres in regulating both stability of genome and replicative immortality seem to contribute in essential ways in cancer initiation and progression. It is concluded that activity of telomerase can be used as a biomarker for diagnosis of malignant oral cancer and a target for inactivation in chemotherapy or gene therapy. Its expression will also prove to be an important diagnostic tool as well as a novel target for cancer therapy. The activation of telomerase may be an important step in tumorgenesis which can be controlled by inactivating its activity during chemotherapy. The expression and activity of telomerase are indispensable for cancer development. There are no drugs which can effect extremely to treat oral cancers. There is a general call for new emerging drugs or methods that are highly effective towards cancer treatment, possess low toxicity, and have a minor environment impact. Some novel natural products also offer opportunities for innovation in drug discovery. Natural compounds isolated from medicinal plants, as rich sources of novel anticancer drugs, have been of increasing interest with some enzyme (telomerase) blockage property. The alarming reports of cancer cases increase the awareness amongst the clinicians and researchers pertaining to investigate newer drug with low toxicity.

Keywords: oral carcinoma, telomere, telomerase, blockage

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Authors: Maryam Parsian, Pelin Mutlu, Ufuk Gunduz

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Two-dimensional cell culture affords simplicity and low cost, but it has serious limitations; lacking cell-cell and cell-matrix interactions that are present in tissues. Cancer cells grown in 3D culture systems have distinct phenotypes of adhesion, growth, migration, invasion as well as profiles of gene and protein expression. These interactions cause the 3D-cultured cells to acquire morphological and cellular characteristics relevant to in vivo tumors. Palbociclib is a chemotherapeutic agent for the treatment of ER-positive and HER-negative metastatic breast cancer. Poly-amidoamine (PAMAM) dendrimer is a well-defined, special three-dimensional structure and has a multivalent surface and internal cavities that can play an essential role in drug delivery systems. In this study, palbociclib is loaded onto the magnetic PAMAM dendrimer. Hanging droplet method was used in order to form 3D spheroids. The possible toxic effects of both free drug and drug loaded nanoparticles were evaluated in 2D and 3D MCF-7, MD-MB-231 and SKBR-3 breast cancer cell culture models by performing MTT cell viability and Alamar Blue assays. MTT analysis was performed with six different doses from 1000 µg/ml to 25 µg/ml. Drug unloaded PAMAM dendrimer did not demonstrate significant toxicity on all breast cancer cell lines. The results showed that 3D spheroids are clearly less sensitive than 2D cell cultures to free palbociclib. Also, palbociclib loaded PAMAM dendrimers showed more toxic effect than free palbociclib in all cell lines at 2D and 3D cultures. The results suggest that the traditional cell culture method (2D) is insufficient for mimicking the actual tumor tissue. The response of the cancer cells to anticancer drugs is different in the 2D and 3D culture conditions. This study showed that breast cancer cells are more resistant to free palbociclib in 3D cultures than in 2D cultures. However, nanoparticle loaded drugs can be more cytotoxic when compared to free drug.

Keywords: 2D and 3D cell culture, breast cancer, palbociclibe, PAMAM magnetic nanoparticles

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Authors: Bouami Hind, Millot Patrick

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The implementation of automated devices in life-critical systems such as hospitals can bring a new set of challenges related to automation malfunctions. While automation has been identified as great leverage for the medication dispensing system’s security and efficiency, it also increases the complexity of the organization. In particular, the installation and operation stage of automated devices can be complex when malfunctions related to automated systems occur. This paper aims to document operators’ situation awareness about the malfunctions of automated drug delivery systems (ADCs) during their implementation through Saint Brieuc hospital’s feedback. Our evaluation approach has been deployed in Saint Brieuc hospital center’s pharmacy, which has been equipped with automated nominative drug dispensing systems since January of 2021. The analysis of Saint Brieuc hospital center pharmacy’s automation revealed numerous malfunctions related to the implementation of Automated Delivery Cabinets. It appears that the targeted performance is not reached in the first year of implementation in this case study. Also, errors have been collected in patients' automated treatments’ production such as lack of drugs in pill boxes or nominative carnets, excess of drugs, wrong location of the drug, drug blister damaged, non-compliant sachet, or ticket errors. Saint Brieuc hospital center’s pharmacy is doing a tremendous job of setting up and monitoring performance indicators from the beginning of automation and throughout ADC’s operation to control ADC’s malfunctions and meet the performance targeted by the hospital. Health professionals, including pharmacists, biomedical engineers and directors of work, technical services and safety, are heavily involved in an automation project. This study highlights the importance of the evaluation of ADCs’ performance throughout the implementation process and the hospital’s team involvement in automation supervision and management.

Keywords: life-critical systems, situation awareness, automated delivery cabinets, implementation, risks and malfunctions

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Authors: Yen-Hao Su, Wan-Chun Tang, Ya-Wen Cheng, Peik Sia, Chi-Chen Huang, Yi-Chao Lee, Hsin-Yi Jiang, Ming-Heng Wu, I-Lu Lai, Jun-Wei Lee, Kuen-Haur Lee

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There is a wide range of drugs and combinations under investigation and/or approved over the last decade to treat colorectal cancer (CRC), but the 5-year survival rate remains poor at stages II–IV. Therefore, new, more efficient drugs still need to be developed that will hopefully be included in first-line therapy or overcome resistance when it appears, as part of second- or third-line treatments in the near future. In this study, we revealed that heat shock protein 90 (Hsp90) inhibitors have high therapeutic potential in CRC according to combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and chemical genomic database of Connectivity Map (CMap). We found that second generation Hsp90 inhibitor, NVP-AUY922, significantly down regulated the activities of a broad spectrum of kinases involved in regulating cell growth arrest and death of NVPAUY922-sensitive CRC cells. To overcome NVP-AUY922-induced upregulation of survivin expression which causes drug insensitivity, we found that combining berberine (BBR), a herbal medicine with potency in inhibiting survivin expression, with NVP-AUY922 resulted in synergistic antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells. Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells with the combination of NVP-AUY922 and BBR caused cell growth arrest through inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1–β-catenin–cyclin D1 signaling pathway. Finally, we found that the expression level of Hsp90 in tumor tissues of CRC was positively correlated with CDK4 and Pin1 expression levels. Taken together, these results indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple oncogenic signaling pathways of CRC.

Keywords: berberine, colorectal cancer, connectivity map, heat shock protein 90 inhibitor

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Authors: Syed Beenish Rufai, Sarman Singh

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Background: Performance of Genotype MTBDRsl (Hain Life science GmbH Germany) for detection of mutations associated with second-line drug resistance is well known. However, less evidence regarding the association of mutations and genetic background of strains is known which, in the future, is essential for clinical management of anti-tuberculosis drugs in those settings where the probability of particular genotype is predominant. Material and Methods: During this retrospective study, a total of 259 MDR-TB isolates obtained from pulmonary TB patients were tested for second-line drug susceptibility testing (DST) using Genotype MTBDRsl VER 1.0 and compared with BACTEC MGIT-960 as a reference standard. All isolates were further characterized using spoligotyping. The spoligo patterns obtained were compared and analyzed using SITVIT_WEB. Results: Of total 259 MDR-TB isolates which were screened for second-line DST by Genotype MTBDRsl, mutations were found to be associated with gyrA, rrs and emb genes in 82 (31.6%), 2 (0.8%) and 90 (34.7%) isolates respectively. 16 (6.1%) isolates detected mutations associated with both FQ as well as to AG/CP drugs (XDR-TB). No mutations were detected in 159 (61.4%) isolates for corresponding gyrA and rrs genes. Genotype MTBDRsl showed a concordance of 96.4% for detection of sensitive isolates in comparison with second-line DST by BACTEC MGIT-960 and 94.1%, 93.5%, 60.5% and 50% for detection of XDR-TB, FQ, EMB, and AMK/CAP respectively. D94G was the most prevalent mutation found among (38 (46.4%)) OFXR isolates (37 FQ mono-resistant and 1 XDR-TB) followed by A90V (23 (28.1%)) (17 FQ mono-resistant and 6 XDR-TB). Among AG/CP resistant isolates A1401G was the most frequent mutation observed among (11 (61.1%)) isolates (2 AG/CP mono-resistant isolates and 9 XDR-TB isolates) followed by WT+A1401G (6 (33.3%)) and G1484T (1 (5.5%)) respectively. On spoligotyping analysis, Beijing strain (46%) was found to be the most predominant strain among pre-XDR and XDR TB isolates followed by CAS (30%), X (6%), Unique (5%), EAI and T each of 4%, Manu (3%) and Ural (2%) respectively. Beijing strain was found to be strongly associated with D94G (47.3%) and A90V mutations by (47.3%) and 34.8% followed by CAS strain by (31.6%) and 30.4% respectively. However, among AG/CP resistant isolates, only Beijing strain was found to be strongly associated with A1401G and WT+A1401G mutations by 54.5% and 50% respectively. Conclusion: Beijing strain was found to be strongly associated with the most prevalent mutations among pre-XDR and XDR TB isolates. Acknowledgments: Study was supported with Grant by All India Institute of Medical Sciences, New Delhi reference No. P-2012/12452.

Keywords: tuberculosis, line probe assay, XDR TB, drug susceptibility

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Authors: Melissa Mattos, Camila Lima, Ibraim Castro, Augusto Carioca, Saulo Magalhães, Paula Freitas, Keciany Oliveira

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Obesity is a chronic, multifactorial, relapsing disease that has increased dramatically over the years. Its control is considered a public health issue, and more and more treatments and interventions are being studied to reduce its prevalence. When interventions in lifestyle and the use of drugs do not generate lasting results, bariatric procedures emerge as a resource for obesity control. The main guidelines for the treatment of obesity emphasize the need for pre-procedure and post-procedure nutritional monitoring to avoid nutritional deficiencies that may occur. The individual who undergoes bariatric surgery needs to understand the changes that will be necessary for life in view of the intense anatomical and metabolic changes that result from surgical techniques. To assess the nutritional profile of patients who undergo bariatric surgery, we analyzed data from the medical records of all people who underwent sleeve-type bariatric surgery from January to June 2022 at a clinic in the City of Fortaleza. 38 patients were analyzed, 32 women and 6 men in the pre-surgical period, 6 and 12 months after surgery. The data showed an average weight loss of 24.45% at 6 months and 30.85% at 12 months, with a reduction of 21.32% and 30.41%, respectively, in the fat percentage, also indicating that 13.15% used drugs for weight loss during this period, leading to reflection on the isolated long-term efficacy of bariatric surgery, requiring multidisciplinary follow-up for a change in lifestyle. Only 12 individuals, corresponding to 31.57%, reached eutrophic BMI 12 months after surgery, 20 individuals remained overweight, corresponding to 52.63% of the sample, and 6 individuals (15.78%) remained in the BMI obese class I. As for body composition, there was a 52.39% reduction in fat mass and a 12.82% reduction in muscle mass, and 21% of individuals underwent cholecystectomy. Sleeve-type bariatric surgery promoted significant weight loss after 1 year of the procedure, with a reduction in body fat percentage and fat mass. Most patients were still overweight and had a significant reduction in muscle mass.

Keywords: bariatric surgery, sleeve gastrectomy, obesity, sleeve

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Authors: Mireille Canal-Raffin, Nadege Lepage, Antoine Villa

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Context: Most antineoplastic drugs (AD) have a potential carcinogenic, mutagenic and/or reprotoxic effect and are classified as 'hazardous to handle' by National Institute for Occupational Safety and Health Their handling increases with the increase of cancer incidence. AD contamination from workers who handle AD and/or care for treated patients is, therefore, a major concern for occupational physicians. As part of the process of evaluation and prevention of chemical risks for professionals exposed to AD, Biological Monitoring of Occupational Exposure (BMOE) is the tool of choice. BMOE allows identification of at-risk groups, monitoring of exposures, assessment of poorly controlled exposures and the effectiveness and/or wearing of protective equipment, and documenting occupational exposure incidents to AD. This work aims to make proposals for the practical implementation of the BMOE for AD. The proposed strategy is based on the French good practice recommendations for BMOE, issued in 2016 by 3 French learned societies. These recommendations have been adapted to occupational exposure to AD. Results: AD contamination of professionals is a sensitive topic, and the BMOE requires the establishment of a working group and information meetings within the concerned health establishment to explain the approach, objectives, and purpose of monitoring. Occupational exposure to AD is often discontinuous and 2 steps are essential upstream: a study of the nature and frequency of AD used to select the Biological Exposure Indice(s) (BEI) most representative of the activity; a study of AD path in the institution to target exposed professionals and to adapt medico-professional information sheet (MPIS). The MPIS is essential to gather the necessary elements for results interpretation. Currently, 28 urinary specific BEIs of AD exposure have been identified, and corresponding analytical methods have been published: 11 BEIs were AD metabolites, and 17 were AD. Results interpretation is performed by groups of homogeneous exposure (GHE). There is no threshold biological limit value of interpretation. Contamination is established when an AD is detected in trace concentration or in a urine concentration equal or greater than the limit of quantification (LOQ) of the analytical method. Results can only be compared to LOQs of these methods, which must be as low as possible. For 8 of the 17 AD BEIs, the LOQ is very low with values between 0.01 to 0.05µg/l. For the other BEIs, the LOQ values were higher between 0.1 to 30µg/l. Results restitution by occupational physicians to workers should be individual and collective. Faced with AD dangerousness, in cases of workers contamination, it is necessary to put in place corrective measures. In addition, the implementation of prevention and awareness measures for those exposed to this risk is a priority. Conclusion: This work is a help for occupational physicians engaging in a process of prevention of occupational risks related to AD exposure. With the current analytical tools, effective and available, the (BMOE) to the AD should now be possible to develop in routine occupational physician practice. The BMOE may be complemented by surface sampling to determine workers' contamination modalities.

Keywords: antineoplastic drugs, urine, occupational exposure, biological monitoring of occupational exposure, biological exposure indice

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Authors: Yuvraj Singh Dangi, Brajesh Kumar Tiwari, Ashok Kumar Jain, Kamta Prasad Namdeo

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The potential use of liposomes as drug carriers by i.v. injection is limited by their low stability in blood stream. Firstly, phospholipid exchange and transfer to lipoproteins, mainly HDL destabilizes and disintegrates liposomes with subsequent loss of content. To avoid the pain associated with injection and to obtain better patient compliance studies concerning various dosage forms, have been developed. Conventional liposomes (unilamellar and multilamellar) have certain drawbacks like low entrapment efficiency, stability and release of drug after single breach in external membrane, have led to the new type of liposomal systems. The challenge has been successfully met in the form of Double Liposomes (DL). DL is a recently developed type of liposome, consisting of smaller liposomes enveloped in lipid bilayers. The outer lipid layer of DL can protect inner liposomes against various enzymes, therefore DL was thought to be more effective than ordinary liposomes. This concept was also supported by in vitro release characteristics i.e. DL formation inhibited the release of drugs encapsulated in inner liposomes. DL consists of several small liposomes encapsulated in large liposomes, i.e., multivesicular vesicles (MVV), therefore, DL should be discriminated from ordinary classification of multilamellar vesicles (MLV), large unilamellar vesicles (LUV), small unilamellar vesicles (SUV). However, for these liposomes, the volume of inner phase is small and loading volume of water-soluble drugs is low. In the present study, the potential of phosphatidylethanolamine (PE) lipid anchored double liposomes (DL) to incorporate two drugs in a single system is exploited as a tool to augment the H. pylori eradication rate. Preparation of DL involves two steps, first formation of primary (inner) liposomes by thin film hydration method containing one drug, then addition of suspension of inner liposomes on thin film of lipid containing the other drug. The success of formation of DL was characterized by optical and transmission electron microscopy. Quantitation of DL-bacterial interaction was evaluated in terms of percent growth inhibition (%GI) on reference strain of H. pylori ATCC 26695. To confirm specific binding efficacy of DL to H. pylori PE surface receptor we performed an agglutination assay. Agglutination in DL treated H. pylori suspension suggested selectivity of DL towards the PE surface receptor of H. pylori. Monotherapy is generally not recommended for treatment of a H. pylori infection due to the danger of development of resistance and unacceptably low eradication rates. Therefore, combination therapy with amoxicillin trihydrate (AMOX) as anti-H. pylori agent and ranitidine bismuth citrate (RBC) as antisecretory agent were selected for the study with an expectation that this dual-drug delivery approach will exert acceptable anti-H. pylori activity.

Keywords: Helicobacter pylorI, amoxicillin trihydrate, Ranitidine Bismuth citrate, phosphatidylethanolamine, multi vesicular systems

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Authors: K. A. Laptinskiy, S. A. Burikov, A. M. Vervald, S. A. Dolenko, T. A. Dolenko

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The article presents the results of the application of artificial neural networks to separate the fluorescent contribution of nanodiamonds used as biomarkers, adsorbents and carriers of drugs in biomedicine, from a fluorescent background of own biological fluorophores. The principal possibility of solving this problem is shown. Use of neural network architecture let to detect fluorescence of nanodiamonds against the background autofluorescence of egg white with high accuracy - better than 3 ug/ml.

Keywords: artificial neural networks, fluorescence, data aggregation, biomarkers

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Authors: Leila Baghaarabani, Parvin Razzaghi, Mennatolla Magdy Mostafa, Ahmad Albaqsami, Al Warith Al Rushaidi, Masoud Al Rawahi

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Predicting the interaction between drugs and their molecular targets is pivotal for advancing drug development processes. Due to the time and cost limitations, computational approaches have emerged as an effective approach to drug-target interaction (DTI) prediction. Most of the introduced computational based approaches utilize the drug molecule and protein sequence as input. This study does not only utilize these inputs, it also introduces a protein representation developed using a masked protein language model. In this representation, for every individual amino acid residue within the protein sequence, there exists a corresponding probability distribution that indicates the likelihood of each amino acid being present at that particular position. Then, the similarity between each pair of amino acids is computed to create a similarity matrix. To encode the knowledge of the similarity matrix, Bi-Level Routing Attention (BiFormer) is utilized, which combines aspects of transformer-based models with protein sequence analysis and represents a significant advancement in the field of drug-protein interaction prediction. BiFormer has the ability to pinpoint the most effective regions of the protein sequence that are responsible for facilitating interactions between the protein and drugs, thereby enhancing the understanding of these critical interactions. Thus, it appears promising in its ability to capture the local structural relationship of the proteins by enhancing the understanding of how it contributes to drugprotein interactions, thereby facilitating more accurate predictions. To evaluate the proposed method, it was tested on two widely recognized datasets: Davis and KIBA. A comprehensive series of experiments was conducted to illustrate its effectiveness in comparison to cutting edge techniques.

Keywords: BiFormer, transformer, protein language processing, self-attention mechanism, binding affinity, drug target interaction, similarity matrix, protein masked representation, protein language model

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Authors: Anshu Gupta, Charu Gupta

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Background: Punjab, a border state in India has achieved notoriety world over for its drug abuse problem. People right from school kids to elderly are hooked to drugs. This pattern of substance abuse is prevalent in both cities and villages alike. Excess of younger population in India has further aggravated the situation. It is feared that the benefits of India’s economic growth may well be negated by the rising substance abuse especially in this part of the country. It is quite evident that the pattern of substance abuse tends to change over time which is an impediment in the formulation of effective strategies to tackle this issue. Aim: Purpose of the study was to ascertain the change in the pattern of drug abuse for two consecutive years in the out patient department (OPD) population. Method: The study population comprised of all the patients reporting for deaddiction to the psychiatry outpatient department over a period of twelve months for two consecutive years. All the patients were evaluated by the International Classification of Diseases; 10 criteria for substance abuse/dependence. Results: A considerably high prevalence of substance abuse was present in the Indian population. In general, there was an increase in prevalence from first to the second year, especially among the female population. Increase in prevalence of substance abuse appeared to be more prominent among the younger age group of both the sexes. A significant increase in intravenous drug abuse was observed. Peer pressure and parental imitation were the major factors fueling substance abuse. Precipitation or fear of withdrawal symptoms was the major factor preventing abstinence. Substance abuse had a significant effect on the health and interpersonal relations of these patients. Summary/Conclusion: Drug abuse and addiction are on the rise throughout India. Changing cultural values, increasing economic stress and dwindling supportive bonds appear to be leading to initiation of substance abuse. Need of the hour is to formulate a comprehensive strategy to bring about an overall reduction in the use of drugs.

Keywords: deaddiction, peer pressure, parental imitation, substance abuse/dependance

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